Pembrolizumab in Combination With R-ICE Chemotherapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma

Sponsor
University of Southampton
Study ID
NCT05221645
Phase
PHASE2
Status
Active Not Recruiting

Conditions

  • Diffuse Large B Cell Lymphoma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Pembrolizumab — DRUG
    Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD 1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). Based on preclinical in vitro data, pembrolizumab has high affinity and potent receptor blocking activity for PD 1. Pembrolizumab has an acceptable preclinical safety profile and is in clinical development as an intravenous (IV) immunotherapy for advanced malignancies. Keytruda® (pembrolizumab) is indicated for the treatment of patients across a number of indications because of its mechanism of action to bind the PD-1 receptor on the T cell.
  • Rituximab — DRUG
    Rituximab is a chimeric mouse/human monoclonal antibody that binds to CD20, on pre-B and mature B lymphocytes and eliminates these cells potentially via a number of different mechanisms. Anti-CD20 mAbs, like rituximab, are classified by their CD20-binding characteristics, ability to induce complement-dependent cytotoxicity (CDC), and immune effector cell effects.
  • Ifosfamide — DRUG
    Ifosfamide, Carboplatin and Etoposide (ICE) is proven to be an effective regimen in the relapsed refractory NHL population. In a study of 163 transplant eligible patients with relapsed/refractory disease, 66.3% of patients obtained CR/PR after 3 cycles of ICE chemotherapy at two weekly intervals.
  • Carboplatin — DRUG
    Ifosfamide, Carboplatin and Etoposide (ICE) is proven to be an effective regimen in the relapsed refractory NHL population. In a study of 163 transplant eligible patients with relapsed/refractory disease, 66.3% of patients obtained CR/PR after 3 cycles of ICE chemotherapy at two weekly intervals.
  • Etoposide — DRUG
    Ifosfamide, Carboplatin and Etoposide (ICE) is proven to be an effective regimen in the relapsed refractory NHL population. In a study of 163 transplant eligible patients with relapsed/refractory disease, 66.3% of patients obtained CR/PR after 3 cycles of ICE chemotherapy at two weekly intervals.

Study Details

This is an open-label, multicentre, randomised phase II trial in relapsed or refractory diffuse large B-cell lymphoma.

Key Dates

Start date
Jun 27, 2022
Status verified
Feb 2026
Primary completion
May 30, 2026
Completion
Dec 31, 2026

Study Design

Enrollment
65 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Control Arm A
    Patients will receive three cycles of R-ICE. Each cycle is 21 days +/- 3 days Rituximab 375mg/m2 Ifosfamide 5,000mg/m2 Carboplatin AUC = 5 (max dose 800mg) Etoposide 100mg/m2 All patients who are deemed to be in CR or PR on the post treatment PET-CT scan will undergo autologous stem cell transplant (ASCT) within 4 weeks of completing R-ICE treatment. BEAM (carmustine, etoposide, cytarabine and melphalan) conditioning will be employed according to institutional protocol.
  • Experimental: Experimental Arm B
    Pembrolizumab 200mg Rituximab 375mg/m2 Ifosfamide 5,000mg/m2 Carboplatin AUC = 5 (max dose 800mg) Etoposide 100mg/m2 Patients will receive up to 3 cycles of: P+R-ICE, where each cycle is 21 days long +/-\_3 days. All patients who are deemed to be in CR or PR on the post treatment PET-CT scan will undergo autologous stem cell transplant (ASCT) within 4 weeks of completing P+R-ICE treatment. BEAM (carmustine, etoposide, cytarabine and melphalan) conditioning will be employed according to institutional protocol. These patients will then be offered maintenance pembrolizumab every 3 weeks for one year.

Primary Outcome Measure

To establish the event-free survival at 1 year in patients treated with P+R-ICE [ Time Frame: 12 months ]

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